Differential activation of platelet phospholipases by thrombin and ionophore A23187.
Although exposure of platelets to ionophore A23187 causes some activation of phospholipase C, ionophore is an inefficient stimulus for this enzyme. A23187 induces the formation of one-fourth to one-sixth as much diglyceride as does thrombin when comparable amounts of phosphatidylinositol are hydrolyzed. We have shown previously that in the presence of indomethacin thrombin-treated platelets accumulate significant quantitites of diglyceride via inhibition of diglyceride lipase. However, a similar accumulation of diglyceride does not occur when ionophore is used as a stimulus in the presence of indomethacin. Ionophore does not appear to be stimulating the catabolism of diglyceride, since the simultaneous addition of ionophore and thrombin does not impair the formation and metabolism of diglyceride which is promoted by thrombin alone. Further, whereas indomethacin exerts no inhibitory effects upon phospholipase C or the formation of diglyceride in platelets responding to either stimulus, indomethacin does inhibit 1) the loss of arachidonic acid from phosphatidylcholine in response to thrombin and 2) the loss of arachidonic acid from phosphatidylcholine and phosphatidylinositol in response to A23187. We conclude that in A23187-activated platelets, phosphatidylinositol is hydrolyzed primarily by an enzyme other than phospholipase C. This indomethacin-inhibitable enzyme is probably a phospholipase A. Therefore, the full expression of phospholipase C in platelets requires more than a general flux in intracellular calcium.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology*; D004075:Diglycerides / Q000097:blood; D004789:Enzyme Activation; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D010740:Phospholipases / Q000097:blood*; D010743:Phospholipids / Q000097:blood; D013917:Thrombin / Q000502:physiology*; D013929:Thromboxane B2 / Q000494:pharmacology; D010738:Type C Phospholipases / Q000097:blood*
D000900:Anti-Bacterial Agents; D001095:Arachidonic Acids; D004075:Diglycerides; D010743:Phospholipids; D000001:Calcimycin; D013929:Thromboxane B2; D010740:Phospholipases; D010738:Type C Phospholipases; D013917:Thrombin; D007213:Indomethacin